The goal of this interventional clinical research study is to assess the efficacy of a 12-week precision exercise training intervention to improve exercise tolerance in sepsis survivors.

The main question it aims to answer is does a 12-week precision exercise training program improve constant load exercise time in sepsis survivors?

Participants will:

• Answer questionnaires related to patient reported outcomes and give a blood sample
• Perform a constant load exercise test
• Complete 12-weeks (3 x per week, 36 session in total) of precision exercise training consisting of individualized, nonlinear periodized strength and aerobic exercise training.

Researchers will compare the exercise group to an attention control group of sepsis survivors who do not receive exercise training but instead undergo usual care procedures and receive general lifestyle advice 1x per week.

Sepsis is a life threatening condition that results in multi-organ system dysfunction. In those who survive sepsis, many patients present with chronic immune dysregulation (i.e., paradoxical hyperinflammation and immune suppression), leading to high rates of re-hospitalization. In addition, exercise tolerance is significantly reduced both acutely post hospital discharge and long term (~5 years post initial infection). Exercise training is a pleiotropic intervention that has been demonstrated to improve exercise tolerance in a multitude of clinical populations. Aerobic exercise training is also associated with anti-inflammatory and immune-enhancing effects; however, the magnitude of these immunological adaptations is largely dependent on the exercise prescription used. To date, exercise training studies in sepsis have used a more traditional generic linear exercise training approach, which has resulted in minimal or no effect on exercise tolerance. This is in contrast to other clinical populations wherein precision exercise training (e.g., individualized, nonlinear periodized, combined aerobic and strength training) has resulted in greater improvements in exercise tolerance compared to non-specific linear exercise programs, and is considered safe and tolerable. To date, no study has sought to investigate the effects of a precision exercise training intervention on exercise tolerance and immune function in sepsis survivors.

Inclusion Criteria:

• Signed informed consent
• At least 19 years of age
• ≥60 days prior to study enrollment, known or suspected infection that includes at least two of the following clinical criteria that together constitute a new bedside clinical score termed quickSOFA (qSOFA): respiratory rate >22breaths/min, altered mentation, or systolic blood pressure <100mmHg.
• Cardiorespiratory fitness <80% of age and sex-predicted norms
• Can commit to attending 3 exercise sessions a week for 12-weeks

Exclusion Criteria:

• Unable to provide informed consent
• On supplemental oxygen
• Known previous cardiac or cerebral vascular events in the past 90 days
• Diabetes
• Autoimmune diseases or on daily immunomodulatory drugs
• Obstructive sleep apnea
• Uncontrolled hypertension
• Known pregnancy/ intending to get pregnant within 28 days of enrolling in the study or breastfeeding
• Desaturation during exercise SpO2<85%
• Cardiovascular contraindication or musculoskeletal limitations to exercise as assessed during the cardiopulmonary exercise test

Deidentified individual participant data will be made available as required by a condition of awards and agreements supporting the research.

12 months after publication and for up to 36 months post publication

The investigator who proposed to use the data and upon reasonable request. Requests should be directed to graeme.koelwyn@hli.ubc.ca. To gain access, data requestors will need to sign a data access agreement.